ASP Scan (Weekly) for Oct 11, 2019

Probiotics and C diff risk
MCR genes on Algerian farms
Price cut demand for MDR-TB drug
ICU infections in Europe
XDR typhoid in travelers
Post-hospital antibiotic use
Resistant gonorrhea response plan
Urinary antigen testing for pneumonia
C diff testing guidelines challenged
XDR Klebsiella pneumoniae

Probiotics associated with increased C difficile risk in NY hospital study

Patients who received probiotics concurrently with antibiotics were more likely to have an incident of Clostridioides difficile infection (CDI) than those who didn't receive probiotics, researchers reported yesterday in the American Journal of Infection Control.

The retrospective study analyzed a cohort of patients at NYU Winthrop Hospital who received at least one dose of antibiotics associated with a high risk of inducing CDI, including some who were on or started probiotics when antibiotics were administered. While it is common in hospitals to administer probiotics concomitantly with antibiotics based on the theory that they might prevent CDI, there is conflicting evidence that probiotics have this benefit. To determine whether probiotics are effective as CDI prophylaxis, the researchers grouped patients according to probiotic use and examined the association between probiotic use and incident CDI.

Of the 3,266 patients analyzed, 167 (5.1%) received probiotics within 24 hours of antibiotic initiation, and an additional 216 (6.6%) received probiotics during the 12-week follow-up period. A total of 150 patients (4.6%) had CDI within 12 weeks of antibiotic initiation.

Of those patients who initiated probiotic use on or before the start of antibiotics, 9.6% had an incident CDI within 12 weeks compared with 4.2% of those not on probiotics at the start of their antibiotics (relative risk, 2.3; 95% confidence interval [CI], 1.4 to 3.7; P = .001). In time-dependent Cox models accounting for probiotic initiation and adjusting for potential confounders, a positive association between probiotics and CDI remained significant (hazard ratio, 2.7; 95% CI, 1.74 to 4.08; P < .001).

Use of proton pump inhibitors and histamine 2 receptor antagonists was also associated with an increased risk of CDI, as was the administration of several antibiotics simultaneously. Sex and age were not found to have a significant impact on CDI incidence.

"Although our finding of increased CDI in those patients who took probiotics was unexpected, patients are vulnerable to CDI when their bowel flora is disrupted," the authors of the study write. "Perhaps further disruption with various bacterial species thought to be protective is, in fact, equally disruptive and potentially harmful."

Based on the findings, the authors do not recommend administration of probiotics to prevent CDI.
Oct 10 Am J Infect Control study


MCR genes found in soil, water, manure on Algerian farms

Environmental sampling conducted on farms in northwest Algeria has detected strains of Escherichia coli carrying colistin-resistance genes, French and Algerian researchers reported yesterday in the Journal of Global Antimicrobial Resistance.

Of the 40 environmental samples collected from eight farms, 103 colistin-resistant bacterial strains were isolated from agricultural soil, irrigation water, and horse, sheep, and cow manure. Further analysis identified eight of the strains as E coli, including six carrying the MCR-1 gene and two carrying the MCR-3 gene.

All E coli strains were non-susceptible to amoxicillin, amoxicillin-clavulanate, ticarcillin, nalidixic acid, ciprofloxacin, gentamicin, trimethoprim-sulfamethoxazole, and rifampicin. Two of the strains were also non-susceptible to cefotaxim, cefepim, and aztreonam and were carrying the extended-spectrum beta-lactamase gene blaTEM-12 in addition to MCR-1.

The 6 E coli isolates carrying the MCR-1 gene were assigned to three sequences types (STs), including ST10 (n = 3), ST405 (n = 2) and ST345 (n = 1), whereas the two strains carrying MCR-3 gene were assigned to ST155.

The authors of the study say the findings suggest farms could be an important reservoir of colistin-resistant E coli, and that the transfer of bacteria from animal manure to soil and irrigation water has the potential to spread multidrug-resistant pathogens.
Oct 10 J Glob Antimicrob Resist abstract


MSF calls for price cut on multidrug-resistant TB drug

Originally published by CIDRAP News Oct 10

Doctors Without Borders/Médecins sans Frontières (MSF) is calling on drug maker Johnson & Johnson to lower the price of bedaquilin, an oral medication for the treatment of patients with multidrug-resistant tuberculosis (MDR-TB).

Arguing that the drug was developed and tested in collaboration with the TB research community and treatment providers like MSF, using taxpayer money and contributions from other donors, the medical humanitarian organization is demanding that Johnson & Johnson—which owns the patent on bedaquiline—cut the price to $1 a day, roughly half of what the company currently charges.

"Those who contributed to bedaquiline's development should have a say in how the drug is priced," Sharonann Lynch, HIV and TB policy advisor for MSF's Access Campaign, said in a press release. "We will not back down until the price of bedaquiline is brought down." 

Bedaquiline is a core drug in the all-oral treatment regimen currently recommended by the World Health Organization (WHO) for patients with MDR-TB. The previous regimen included injectable drugs associated with serious side effects and increasing treatment failure. In a move that was widely hailed by MSF and other TB advocacy and global health groups, the WHO added bedaquiline as a first-line treatment in 2018, but MSF says fewer than 12,000 people have been treated with a regimen including bedaquiline since that change was made.

MSF says the lowest price Johnson & Johnson  charges for 20 months of bedaquiline is nearly $1,200, or $2 per day, a price the organization believes is preventing scale-up of the drug in countries struggling with MDR-TB epidemics.
Oct 10 MSF press release


European report highlights resistance levels in ICU-associated infections

Originally published by CIDRAP News Oct 10

The European Centre for Disease Prevention and Control (ECDC) today issued a new report highlighting the widespread problem of healthcare-associated infections (HAIs) in European intensive care units (ICUs).

The report, based on 2017 data submitted to the European Surveillance System by 14 European Union/European Economic Activity (EU/EEA) countries, shows that 11,787 (8.3%) of the 142,805 patients who stayed in an ICU for more than 2 days presented with at least one HAI.

Documented HAIs included 8,983 cases of pneumonia, 5,298 cases of bloodstream infection (BSI), and 1,274 urinary tract infections (UTIs). Ninety-seven percent of pneumonia cases were associated with intubation, 37% of BSIs were catheter related, and 98% of UTIs were linked to a urinary catheter. The most frequently isolated pathogens were Pseudomonas aeruginosa in pneumonia episodes, coagulase-negative staphylococci in BSIs, and E coli in UTIs.

Among the bacteria associated with ICU-acquired HAIs, 23.5% of Staphylococcus aureus isolates were oxacillin-resistant; 9.5% of Enterococcus isolates were vancomycin-resistant; 26.5% of P aeruginosa isolates were ceftazidime-resistant; and 15.9%, 39.9%, and 34.3% of E coli, Klebsiella pneumoniae, and Enterobacter isolates, respectively, showed resistance to third-generation cephalosporins. Carbapenem resistance was reported in 15.2% of Klebsiella isolates, 25.9% of P aeruginosa isolates, 63.9% of Acinetobacter baumannii isolates, 1.7% of Enterobacter isolates, and 0.8% of E coli isolates.

"This report confirms the importance of antimicrobial resistance in gram-negative bacteria in ICUs in the EU/EEA in 2017, with resistance percentages being comparable to the levels reported in previous years," the ECDC said in the report. "The high percentages of resistance to carbapenems of P. aeruginosa, A. baumannii and K pneumoniae isolates reflect the challenges of treatment of ICU patients, a highly vulnerable patient population."
Oct 10 ECDC report


ECDC, CDC warn of extensively drug-resistant typhoid in Pakistan

Originally published by CIDRAP News Oct 9

Several countries around the world have reported an uptick of extensively drug-resistant (XDR) typhoid fever, the ECDC said in a news release today.

According to the ECDC, recent visitors to Pakistan from the United States, Canada, United Kingdom, Denmark, Taiwan, and Australia have contracted XDR typhoid in Pakistan, a strain unresponsive to most antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, ciprofloxacin, and ceftriaxone. 

In today's release, the ECDC provided details on cases in Ireland. Irish authorities have reported 23 typhoid cases have in 2019, of which 12 involved recent travel to Pakistan. Three of the 12 patients with travel history in Pakistan were infected with XDR strains, the ECDC said.

The US Centers for Disease Control and Prevention (CDC), meanwhile, has issued a level 1 travel alert over XDR typhoid cases tied to travel to Pakistan. 

The CDC recommends all travelers planning a trip to Pakistan get a typhoid fever vaccination at least 2 weeks before traveling. A level 1 "watch" alert is the lowest of the CDC's three stages and means travelers should practice "usual precautions."

Typhoid fever is caused by the bacterium Salmonella Typhi and spreads through contaminated food and water.
Oct 9 ECDC 
news release 
Sep 30 CDC 


Nationwide US data show high levels of post-discharge antibiotic exposure

Originally published by CIDRAP News Oct 8

An analysis of nationwide Veterans Health Administration data across 3 years finds that a large proportion of antimicrobial exposure among hospitalized patients occurs immediately following discharge, according to a study yesterday in Clinical Microbiology and Infection.

The researchers looked at data from 1,681,701 million acute-care admissions in 122 hospitals from 2014 through 2016 and found that 335,369 patients (19.9%) were prescribed an oral antimicrobial drug at discharge. Fluoroquinolones were the most commonly prescribed drug, accounting for 38.3% of the post-discharge antimicrobials, followed by cephalosporins (14.8%) and beta lactam/lactamase inhibitors (14.4%).

In addition, 39% of the total duration of antimicrobial exposure occurred after hospital discharge. And the investigators found that inpatient use of antimicrobials was only weakly correlated with post-discharge antibiotic use.

The researchers say the study is the first nationwide description of oral antimicrobials prescribed on hospital discharge, making it the largest study on the topic. A study in May involving hospitals in the southeastern United States found prolonged antibiotic courses were common at discharge.

The authors of the current study conclude, "Our findings suggest that standard stewardship metrics, which focus entirely on inpatient antimicrobial use, are providing an incomplete assessment of total antimicrobial exposure associated with an acute-care hospital stay."
Oct 7 Clin Microbiol Infect abstract
May 29 CIDRAP News scan on earlier study


European health officials update resistant gonorrhea response plan

Originally published by CIDRAP News Oct 8

The ECDC yesterday published an updated response plan to manage the threat of multidrug- and extensively drug-resistant (MDR and XDR) gonorrhea in Europe.

Noting the rising resistance of Neisseria gonorrhoeae to several antibiotics over the last decade, and the report of an XDR gonorrhea strain in the United Kingdom in 2018, the ECDC said an update to its 2012 response plan was needed to manage the threat of untreatable gonorrhea in Europe. "The present ECDC 2019 response plan strives to further support Member States to develop and implement national strategies and interventions to control the threat of MDR and XDR gonorrhoea in a multidisciplinary approach," the agency said.

The plan calls for EU/EEA member states to strengthen surveillance of gonococcal antimicrobial susceptibility so that MDR and XDR strains can be detected and monitored, ensure that appropriate capacity for culture and susceptibility testing is available, implement suitable treatment failure monitoring procedures so that national and international authorities can develop targeted interventions to prevent the spread of MDR and XDR strains, effectively disseminate results from surveillance to increase awareness among healthcare workers and the public, and introduce strategies to reduce the burden of gonorrhea.

The ECDC says other elements of a comprehensive management strategy should include appropriate treatment, diagnostics, and testing algorithms (such as three-site testing in men who have sex with men), test of cure, notification and treatment of partners, and enhanced focus on risk groups and sexually transmitted infection prevention measures.
Oct 7 ECDC MDR and XDR gonorrhea response plan


Study find urinary antigen testing underused in pneumonia patients

Originally published by CIDRAP News Oct 7

An analysis of almost 160,000 pneumonia patients in 170 US hospitals indicates that urinary antigen testing (UAT), a practice recommended by national guidelines to allow for antibiotic de-escalation in patients with community-acquired pneumonia (CAP), is not widely performed, researchers reported today in Clinical Infectious Diseases.

To determine adherence to UAT recommendations from the Infectious Diseases Society of America (IDSA) and the American Thoracic Society and to gauge whether UAT results affect prescribing behavior, researchers with Cleveland Clinic and the University of Massachusetts Medical School conducted a retrospective study of adult patients with CAP or healthcare-associated pneumonia admitted to 170 hospitals from 2010 through 2015.

Among 159,894 eligible admissions, 24,757 (15.5%) had UAT performed (18.4% of ICU and 15.3% of non-ICU patients). Among hospitals with more than 100 eligible patients, UAT testing proportions ranged from 0%-69%. Compared to patients with negative UAT, 7.2% with positive UAT more often had a positive Streptococcus pneumoniae culture (25.4% vs 1.9%, P < 0.001)—a result that should allow for rapid de-escalation of therapy—and less often had resistant bacteria (5.2% vs 6.8%, P < 0.05).

Of patients initially treated with broad-spectrum antibiotics, most were still receiving broad-spectrum therapy 3 days later, but UAT-positive patients more often had coverage narrowed (38.4% vs 17.0% UAT-negative and 14.6% untested patients, P < 0.001). In addition, the duration of vancomycin, piperacillin-tazobactam, and carbapenems were all shorter in response to a positive UAT. Hospital rate of UAT was strongly correlated with de-escalation following a positive test. Only three patients de-escalated after positive UAT were subsequently admitted to ICU.

The authors conclude, "Despite the test being inexpensive, accurate and rapid, UAT appears underused, but could be an important tool for antibiotic stewardship. Broader indications for testing featured in national guidelines might help to spread its use nationwide."
Oct 7 Clin Infect Dis abstract


Researchers suggest patients on laxatives should be tested for C diff

Originally published by CIDRAP News Oct 7

In another study published in Clinical Infectious Diseases, researchers with Beth Israel Deaconess Medical Center report that the recommendation against conducting CDI stool testing on patients who've recently taken laxatives carries a potential for harm and should be re-evaluated.

To increase the relevance of a positive stool test for C difficile, the 2017 IDSA-Society for Healthcare Epidemiology of America (IDSA-SHEA) clinical guidelines emphasized testing only in patients likely to have true CDI; among the groups the guidelines recommended against testing were those who'd received a laxative in the previous 48 hours. But the authors of the study note that this recommendation rests on weak evidence, and that the guidelines don't define meaningful laxative use or allow room for clinical judgement when other features signal infection.

Out of concern that this recommendation might miss some CDI diagnoses, the researchers prospectively enrolled patients at Beth Israel Deaconess Medical Center with new-onset diarrhea and a positive C difficile nucleic acid amplification (NAAT) test, including patients who'd used a laxative within 48 hours prior to stool testing. They then assessed CDI recurrence and severe outcomes, including intensive care unit (ICU) admission, colectomy, and death, during the 40 days after diagnosis.

Overall, 209 patients with CDI were studied, 65 of whom (31%) had received laxatives. Among the patients receiving versus those not receiving laxatives, there were no significant differences in the proportion meeting severe CDI criteria by four severity scoring methods (66.2% vs 56.3%, respectively, P = 0.224). Similar rates of serious outcomes attributable to CDI, including death, ICU admission, and colectomy, were observed in the laxative and no laxative groups.   

"Had LAX 48 patients been excluded from testing as recommended by the IDSA-SHEA guidelines, diagnosis of CDI would have been missed in nearly one third of this cohort, 66.2% of whom met criteria for severe CDI by IDSA-SHEA scoring methods—including one death, one patient who required a colectomy, and seven patients who required treatment in an ICU due to CDI," the authors write. "It is likely that some of the other LAX 48 patients would also have suffered additional adverse outcomes due to delayed or missed diagnoses and treatment."

The authors say the issue should be investigated in larger multisite studies.
Oct 4 Clin Infect Dis abstract


Germany reports XDR Klebsiella pneumoniae in 4 hospitals

Originally published by CIDRAP News Oct 7

German public health authorities have confirmed a 17-case outbreak of extensively drug-resistant (XDR) K pneunomiae in four hospitals, the ECDC said today in its weekly communicable disease threats report.

Six patients are infected and 11 are carrying XDR K pneumoniae in the northeast state of Mecklenburg-West Pomerania, the ECDC said. The strain is resistant to all penicillins, ephalosporins, carbapenems, quinolones, aminoglycosides, and fosfomycin and colistin, officials said. But it is susceptible to chloramphenicol, tigecycline (though susceptibility is limited), and cefiderocol, an experimental antibiotic not yet approved in Europe.

The outbreak highlights "the worsening situation and the high risk for further spread of highly-resistant, hospital-adapted strains of carbapenem-resistant Enterobacteriaceae in the EU/EEA," the ECDC said. It added that the disease has very few remaining treatment options, and continent-wide enhanced control efforts are needed.

The ECDC said it is monitoring the event and seeking more information from German officials.
Oct 7 ECDC report

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